Transforming growth factor-β activated kinase 1 (TAK1) is a crucial signal transducer in multiple signaling pathways. TAK1 binds TAB1, TAB2, and TAB3, which act as activators and adaptors that specifically regulate the activation of TAK1. To date, the role of TABs is largely unknown in fish. In the present study, a TAB1 cDNA sequence was identified in grouper (Epinephelus coioides), and designated EcTAB1. The full-length open reading frame of EcTAB1 is 1, 521 bp; it encodes 506 amino acids that contains an N-terminal PP2C domain. Many important functional sites in mammalian TAB1 were conserved in TAB1 from grouper and from other fish. Multiple sequence alignment showed that EcTAB1 protein shared high sequence identity with TAB1 of other fish, especially with Stegastes partitus (95% identity). TAB1 was clustered into the same subgroup with other fish TAB1 in the phylogenetic tree. Tissue expression analysis indicated that TAB1 was widely distributed in different tissues. After infection with Cryptocaryon irritans, EcTAB1 expression was up-regulated in the infection site (gills). Besides, EcTAB1 was expressed throughout the grouper spleen (GS) cells and significantly enhanced the activation of NF-κB.